Korsakoff's Syndrome (KS) occurs in alcoholic patients as a result of dietary thiamine deficiency. Long-term thiamine deficiency produces a characteristic pattern of brain damage in restricted areas including the mammillary bodies, medial thalamus, superior coliculus, cerebellar vermis, and vestibular complex. One possible explanation for this pattern of degeneration is that cells in these areas are susceptible to thiamine deficiency because they express different gene products than do non-vulnerable cells. To address this possibility, we are using the technique of differential display to search for mRNAs that are differentially expressed in brain regions which are vulnerable to thiamine deficiency (thalamus, mammillary bodies, etc.) vs. brain areas that are not vulnerable to thiamine deficiency (cortex, striatum, hippocampus). Fragments identified on differential display will be cut from the gel and cloned into plasmid vectors. The expression pattern of the cDNAs will be assessed using RNAse protection and in situ hybridization. cDNAs of interest will be sequenced and compared with sequences in Genbank for homology, and novel cDNAs used to isolate full- length cDNAs for identification. Formerly titled: "Genetic and Neurobiological Factors in Ethanol Sensitivity and Korsakoff Syndrome"